Overcoming preexisting humoral immunity to AAV using capsid decoys

Science Translational Medicine

Volumn 5, Issue 194, 2013, Pages

  Mingozzi, Federico ^a,d   Anguela, Xavier M ^a,b   Pavani, Giulia ^a   Chen, Yifeng ^a,b   Davidson, Robert J ^a   Hui, Daniel J ^a   Yazicioglu, Mustafa ^a   Elkouby, Liron ^a,b   Hinderer, Christian J ^a,c   Faella, Armida ^a   Howard, Carolann ^a   Tai, Alex ^a   Podsakoff, Gregory M ^a   Zhou, Shangzhen ^a   Basner Tschakarjan, Etiena ^a   Wright, John Fraser ^a,c   High, Katherine A ^a,b,c  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

^d GÉNÉTHON   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; NEUTRALIZING ANTIBODY;

ADENO ASSOCIATED VIRUS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY TITER; ARTICLE; BINDING SITE; DOSE RESPONSE; GENE TRANSFER; HUMAN; HUMORAL IMMUNITY; IMMUNOGENICITY; MOUSE; NONHUMAN; PREVALENCE; PRIORITY JOURNAL; RECEPTOR BINDING; SIGNAL TRANSDUCTION; TARGET CELL; VIRUS CAPSID;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; CAPSID; DEPENDOVIRUS; GENE TRANSFER TECHNIQUES; HUMANS; IMMUNITY, HUMORAL; MACACA MULATTA; MALE; MICE; MICE, INBRED C57BL; MUTATION; NEUTRALIZATION TESTS;

EID: 84880559842     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3005795     Document Type: Article

References (42)

1. A. C. Nathwani, E. G. Tuddenham, S. Rangarajan, C. Rosales, J. McIntosh, D. C. Linch, P. Chowdary, A. Riddell, A. J. Pie, C. Harrington, J. O'Beirne, K. Smith, J. Pasi, B. Glader, P. Rustagi, C. Y. Ng, M. A. Kay, J. Zhou, Y. Spence, C. L. Morton, J. Allay, J. Coleman, S. Sleep, J. M. Cunningham, D. Srivastava, E. Basner-Tschakarjan, F. Mingozzi, K. A. High, J. T. Gray, U. M. Reiss, A. W. Nienhuis, A. M. Davidoff, Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med. 365, 2357-2365 (2011).
2. C. S. Manno, G. F. Pierce, V. R. Arruda, B. Glader, M. Ragni, J. J. Rasko, M. C. Ozelo, K. Hoots, P. Blatt, B. Konkle, M. Dake, R. Kaye, M. Razavi, A. Zajko, J. Zehnder, P. K. Rustagi, H. Nakai, A. Chew, D. Leonard, J. F. Wright, R. R. Lessard, J. M. Sommer, M. Tigges, D. Sabatino, A. Luk, H. Jiang, F. Mingozzi, L. Couto, H. C. Ertl, K. A. High, M. A. Kay, Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat. Med. 12, 342-347 (2006).
3. H. Li, V. Haurigot, Y. Doyon, T. Li, S. Y. Wong, A. S. Bhagwat, N. Malani, X. M. Anguela, R. Sharma, L. Ivanciu, S. L. Murphy, J. D. Finn, F. R. Khazi, S. Zhou, D. E. Paschon, E. J. Rebar, F. D. Bushman, P. D. Gregory, M. C. Holmes, K. A. High, In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature 475, 217-221 (2011).
4. V. R. Arruda, H. H. Stedman, V. Haurigot, G. Buchlis, S. Baila, P. Favaro, Y. Chen, H. G. Franck, S. Zhou, J. F. Wright, L. B. Couto, H. Jiang, G. F. Pierce, D. A. Bellinger, F. Mingozzi, T. C. Nichols, K. A. High, Peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle as a novel therapy for hemophilia B. Blood 115, 4678-4688 (2010).
5. S. Boutin, V. Monteilhet, P. Veron, C. Leborgne, O. Benveniste, M. F. Montus, C. Masurier, Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: Implications for gene therapy using AAV vectors. Hum. Gene Ther. 21, 704-712 (2010).
6. R. Calcedo, L. H. Vandenberghe, G. Gao, J. Lin, J. M. Wilson, Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J. Infect. Dis. 199, 381-390 (2009).
7. H. Jiang, L. B. Couto, S. Patarroyo-White, T. Liu, D. Nagy, J. A. Vargas, S. Zhou, C. D. Scallan, J. Sommer, S. Vijay, F. Mingozzi, K. A. High, G. F. Pierce, Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 108, 3321-3328 (2006).
8. C. D. Scallan, H. Jiang, T. Liu, S. Patarroyo-White, J. M. Sommer, S. Zhou, L. B. Couto, G. F. Pierce, Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood 107, 1810-1817 (2006).
9. J. F. Wright, Manufacturing and characterizing AAV-based vectors for use in clinical studies. Gene Ther. 15, 840-848 (2008).
10. J. A. Allay, S. Sleep, S. Long, D. M. Tillman, R. Clark, G. Carney, P. Fagone, J. H. McIntosh, A. W. Nienhuis, A. M. Davidoff, A. C. Nathwani, J. T. Gray, Good manufacturing practice production of self-complementary serotype 8 adeno-associated viral vector for a hemophilia B clinical trial. Hum. Gene Ther. 22, 595-604 (2011).
11. F. Mingozzi, M. V. Maus, D. J. Hui, D. E. Sabatino, S. L. Murphy, J. E. Rasko, M. V. Ragni, C. S. Manno, J. Sommer, H. Jiang, G. F. Pierce, H. C. Ertl, K. A. High, CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat. Med. 13, 419-422 (2007).
12. F. Mingozzi, K. A. High, Immune responses to AAV in clinical trials. Curr. Gene Ther. 11, 321-330 (2011).
13. J. D. Finn, D. Hui, H. D. Downey, D. Dunn, G. C. Pien, F. Mingozzi, S. Zhou, K. A. High, Proteasome inhibitors decrease AAV2 capsid derived peptide epitope presentation on MHC class I following transduction. Mol. Ther. 18, 135-142 (2010).
14. G. C. Pien, E. Basner-Tschakarjan, D. J. Hui, A. N. Mentlik, J. D. Finn, N. C. Hasbrouck, S. Zhou, S. L. Murphy, M. V. Maus, F. Mingozzi, J. S. Orange, K. A. High, Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors. J. Clin. Invest. 119, 1688-1695 (2009).
15. S. R. Opie, K. H. Warrington Jr., M. Agbandje-McKenna, S. Zolotukhin, N. Muzyczka, Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding. J. Virol. 77, 6995-7006 (2003).
16. F. Mingozzi, Y. Chen, S. C. Edmonson, S. Zhou, R. M. Thurlings, P. P. Tak, K. A. High, M. J. Vervoordeldonk, Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue. Gene Ther. 20, 417-424 (2013).
17. V. Monteilhet, S. Saheb, S. Boutin, C. Leborgne, P. Veron, M. F. Montus, P. Moullier, O. Benveniste, C. Masurier, A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8. Mol. Ther. 19, 2084-2091 (2011).
18. Q. Xie, W. Bu, S. Bhatia, J. Hare, T. Somasundaram, A. Azzi, M. S. Chapman, The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc. Natl. Acad. Sci. U.S.A. 99, 10405-10410 (2002).
19. G. Benson, G. Auerswald, I. Elezović, T. Lambert, R. Ljung, M. Morfini, E. Remor, S. Z. Salek, Immune tolerance induction in patients with severe hemophilia with inhibitors: Expert panel views and recommendations for clinical practice. Eur. J. Haematol. 88, 371-379 (2012).
20. G. P. Gao, M. R. Alvira, L. Wang, R. Calcedo, J. Johnston, J. M. Wilson, Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl. Acad. Sci. U.S.A. 99, 11854-11859 (2002).
21. F. Mingozzi, N. C. Hasbrouck, E. Basner-Tschakarjan, S. A. Edmonson, D. J. Hui, D. E. Sabatino, S. Zhou, J. F. Wright, H. Jiang, G. F. Pierce, V. R. Arruda, K. A. High, Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver. Blood 110, 2334-2341 (2007).
22. A. C. Nathwani, J. T. Gray, C. Y. Ng, J. Zhou, Y. Spence, S. N. Waddington, E. G. Tuddenham, G. Kemball-Cook, J. McIntosh, M. Boon-Spijker, K. Mertens, A. M. Davidoff, Selfcomplementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood 107, 2653-2661 (2006).
23. A. C. Nathwani, C. Rosales, J. McIntosh, G. Rastegarlari, D. Nathwani, D. Raj, S. Nawathe, S. N. Waddington, R. Bronson, S. Jackson, R. E. Donahue, K. A. High, F. Mingozzi, C. Y. Ng, J. Zhou, Y. Spence, M. B. McCarville, M. Valentine, J. Allay, J. Coleman, S. Sleep, J. T. Gray, A. W. Nienhuis, A. M. Davidoff, Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol. Ther. 19, 876-885 (2011).
24. J. S. Johnson, R. J. Samulski, Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J. Virol. 83, 2632-2644 (2009).
25. D. M. McCarty, H. Fu, P. E. Monahan, C. E. Toulson, P. Naik, R. J. Samulski, Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther. 10, 2112-2118 (2003).
26. G. D. Hurlbut, R. J. Ziegler, J. B. Nietupski, J. W. Foley, L. A. Woodworth, E. Meyers, S. D. Bercury, N. N. Pande, D. W. Souza, M. P. Bree, M. J. Lukason, J. Marshall, S. H. Cheng, R. K. Scheule, Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy. Mol. Ther. 18, 1983-1994 (2010).
27. M. G. Kaplitt, A. Feigin, C. Tang, H. L. Fitzsimons, P. Mattis, P. A. Lawlor, R. J. Bland, D. Young, K. Strybing, D. Eidelberg, M. J. During, Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: An open label, phase I trial. Lancet 369, 2097-2105 (2007).
28. A. M. Maguire, F. Simonelli, E. A. Pierce, E. N. Pugh Jr., F. Mingozzi, J. Bennicelli, S. Banfi, K. A. Marshall, F. Testa, E. M. Surace, S. Rossi, A. Lyubarsky, V. R. Arruda, B. Konkle, E. Stone, J. Sun, J. Jacobs, L. Dell'Osso, R. Hertle, J. X. Ma, T. M. Redmond, X. Zhu, B. Hauck, O. Zelenaia, K. S. Shindler, M. G. Maguire, J. F. Wright, N. J. Volpe, J. W. McDonnell, A. Auricchio, K. A. High, J. Bennett, Safety and efficacy of gene transfer for Leber's congenital amaurosis. N. Engl. J. Med. 358, 2240-2248 (2008).
29. C. S.Manno, A. J. Chew, S. Hutchison, P. J. Larson, R. W. Herzog, V. R. Arruda, S. J. Tai, M. V. Ragni, A. Thompson, M. Ozelo, L. B. Couto, D. G. Leonard, F. A. Johnson, A. McClelland, C. Scallan, E. Skarsgard, A. W. Flake, M. A. Kay, K. A. High, B. Glader, AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 101, 2963-2972 (2003).
30. C. C. Norbury, Drinking a lot is good for dendritic cells. Immunology 117, 443-451 (2006).
31. S. L. Murphy, H. Li, S. Zhou, A. Schlachterman, K. A. High, Prolonged susceptibility to antibodymediated neutralization for adeno-associated vectors targeted to the liver. Mol. Ther. 16, 138-145 (2008).
32. F. Mingozzi, Y. Chen, S. L. Murphy, S. C. Edmonson, A. Tai, S. D. Price, M. E. Metzger, S. Zhou, J. F. Wright, R. E. Donahue, C. E. Dunbar, K. A. High, Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol. Ther. 20, 1410-1416 (2012).
33. J. Mimuro, H. Mizukami, S. Hishikawa, T. Ikemoto, A. Ishiwata, A. Sakata, T. Ohmori, S. Madoiwa, F. Ono, K. Ozawa, Y. Sakata, Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adeno-associated virus 8 vectors. Mol. Ther. 21, 318-323 (2013).
34. H. T. Le, Q. C. Yu, J. M. Wilson, M. A. Croyle, Utility of PEGylated recombinant adeno-associated viruses for gene transfer. J. Control. Release 108, 161-177 (2005).
35. G. K. Lee, N. Maheshri, B. Kaspar, D. V. Schaffer, PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol. Bioeng. 92, 24-34 (2005).
36. G. Gao, L. H. Vandenberghe, M. R. Alvira, Y. Lu, R. Calcedo, X. Zhou, J. M. Wilson, Clades of adeno-associated viruses are widely disseminated in human tissues. J. Virol. 78, 6381-6388 (2004).
37. M. Bartel, D. Schaffer, H. Büning, Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity. Front. Microbiol. 2, 204 (2011).
38. D. Grimm, J. S. Lee, L. Wang, T. Desai, B. Akache, T. A. Storm, M. A. Kay, In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adenoassociated viruses. J. Virol. 82, 5887-5911 (2008).
39. T. Matsushita, S. Elliger, C. Elliger, G. Podsakoff, L. Villarreal, G. J. Kurtzman, Y. Iwaki, P. Colosi, Adeno-associated virus vectors can be efficiently produced without helper virus. Gene Ther. 5, 938-945 (1998).
40. E. Ayuso, F. Mingozzi, J. Montane, X. Leon, X. M. Anguela, V. Haurigot, S. A. Edmonson, L. Africa, S. Zhou, K. A. High, F. Bosch, J. F.Wright, High AAV vector purity results in serotype-and tissueindependent enhancement of transduction efficiency. Gene Ther. 17, 503-510 (2010).
41. S. L. Murphy, A. Bhagwat, S. Edmonson, S. Zhou, K. A. High, High-throughput screening and biophysical interrogation of hepatotropic AAV. Mol. Ther. 16, 1960-1967 (2008).
42. A. C. Nathwani, J. T. Gray, J. McIntosh, C. Y. Ng, J. Zhou, Y. Spence, M. Cochrane, E. Gray, E. G. Tuddenham, A. M. Davidoff, Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood 109, 1414-1421 (2007).